病毒滴度高的双表达位点禽腺病毒4（FAdV-4）：一种有前景的多价家禽疫苗病毒载体
Dual-expression-site fowl adenovirus 4 (FAdV-4) with high viral titer: a promising viral vector for multivalent poultry vaccines.
摘要(中文译文)
禽腺病毒血清型4（FAdV-4）是一种无囊膜双链DNA病毒，基因组大小为43-45 kb，使其成为开发多价禽用疫苗的有前景的病毒载体。然而，有限的基因组研究阻碍了设计能够表达多种外源蛋白同时保持高病毒滴度的重组FAdV-4的策略。本研究构建了三个缺失突变体（rD14AB、rD2042、rD19A），以评估其在病毒复制和致病性中的作用。仅rD2042与野生型FAdV-4相比表现出复制能力和毒力受损。外源基因表达实验表明，D14AB位点的最大插入容量为2349 bp，且该位点需要SV40 poly(A)信号才能实现高效蛋白表达和病毒增殖。相比之下，D19A位点在没有该信号的情况下可耐受长达1257 bp的插入。利用针对野生型CH_JS_2017优化的插入策略，我们对先前报道的非致病性rON1株（携带来自减毒ON1株的Hexon基因）进行了改造，使其在两个独立位点共表达mCherry、eGFP和mTagBFP2。SPF鸡试验验证了该工程病毒在免疫日龄的安全性以及外源基因的遗传稳定性。该重组病毒在携带3606 bp外源序列总量的同时保持了与野生型相当的滴度，凸显了其双位点优势以及作为多价禽用疫苗载体的潜力。
Abstract
Fowl adenovirus serotype 4 (FAdV-4) is a nonenveloped double-stranded DNA virus with a 43-45 kb genome, making it a promising viral vector for developing multivalent poultry vaccines. However, limited genomic studies have hindered the design of strategies for generating recombinant FAdV-4 capable of expressing multiple foreign proteins while maintaining high viral titers. In this study, three deletion mutants (rD14AB, rD2042, rD19A) were generated to assess their roles in viral replication and pathogenicity. Only rD2042 showed impaired replication and virulence compared with wild-type FAdV-4. Foreign gene expression assays demonstrated that the D14AB site had a maximum insertion capacity of 2349 bp, and an SV40 poly(A) signal was required for efficient protein expression and viral propagation at this locus. In contrast, the D19A site tolerated insertions of up to 1257 bp in the absence of this signal. Using the insertion strategy optimized for wild-type CH_JS_2017, we modified the previously reported nonpathogenic rON1 strain (harboring the Hexon gene from the attenuated ON1 strain) to co-express mCherry, eGFP, and mTagBFP2 at the two independent sites. SPF chicken trials verified the safety of the engineered virus at immunization age and the genetic stability of exogenous genes. The recombinant virus maintained wild-type-comparable titers while carrying 3606 bp of total foreign sequences, highlighting its dual-site advantage and potential as a multivalent poultry vaccine vector.
如何引用
AMA
Zhihui Tang, Wenjian Liu, Biao Xu, Dengfei Feng, Shuhui Liu, Wentao Fan, et al. Dual-expression-site fowl adenovirus 4 (FAdV-4) with high viral titer: a promising viral vector for multivalent poultry vaccines.. Veterinary research. 2026; doi:10.1186/s13567-026-01820-z.
APA
Zhihui Tang, Wenjian Liu, Biao Xu, Dengfei Feng, Shuhui Liu, Wentao Fan, et al (2026). Dual-expression-site fowl adenovirus 4 (FAdV-4) with high viral titer: a promising viral vector for multivalent poultry vaccines.. Veterinary research. https://doi.org/10.1186/s13567-026-01820-z
GB/T 7714
Zhihui Tang, Wenjian Liu, Biao Xu, Dengfei Feng, Shuhui Liu, Wentao Fan, et al. Dual-expression-site fowl adenovirus 4 (FAdV-4) with high viral titer: a promising viral vector for multivalent poultry vaccines.[J]. Veterinary research, 2026 doi:10.1186/s13567-026-01820-z.
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